Transdermal granisetron

Abstract

Adhesive patches for the transdermal administration of granisetron, comprise an acrylic adhesive containing non-acidic nucleophilic moieties which substantially increase flux of granisetron across the skin.

1 . An adhesive patch suitable for the transdermal administration of granisetron to a subject in need thereof, said patch comprising:
 an acrylic adhesive containing non-acidic hydroxyl moieties, and   a physiologically effective amount of granisetron loaded in the acrylic adhesive.   
   
   
       2 . A patch according to  claim 1 , wherein the non-acidic hydroxyl moieties are provided by suitably selected comonomers. 
   
   
       3 . A patch according to  claim 2 , wherein said acrylic adhesive comprises:
 50 to 98% w/w of a primary acrylate monomer, and   0.5 to 20% w/w of a monomer containing non-acidic hydroxyl moieties.   
   
   
       4 . A patch according to  claim 3 , containing 50 to 90% w/w of said primary acrylate monomer. 
   
   
       5 . A patch according to  claim 3 , wherein said primary acrylate monomer is either 2-ethylhexyl acrylate or butyl acrylate. 
   
   
       6 . A patch according to  claim 2 , wherein the selected comonomers are selected from the group consisting of substituted acrylates and substituted methacrylates. 
   
   
       7 . A patch according to  claim 6 , wherein the substituted acrylates are selected from the group consisting of hydroxymethyl acrylates, hydroxyethyl acrylates and hydroxypropyl acrylates. 
   
   
       8 . A patch according to  claim 6 , wherein the substituted methacrylates are selected from the group consisting of hydroxymethyl methacrylates and hydroxyethyl methacrylates. 
   
   
       9 . A patch according to  claim 1 , which is pressure sensitive. 
   
   
       10 . A patch according to  claim 1 , adapted to provide a pharmacologically effective amount of granisetron to said subject within about 2 hours after administration thereof. 
   
   
       11 . A patch according to  claim 1 , having up to about 10% by weight of granisetron. 
   
   
       12 . A patch according to  claim 11 , having less than 8% w/w granisetron. 
   
   
       13 . A patch according to  claim 1 , having a level of granisetron above 4% w/w. 
   
   
       14 . A patch according to  claim 1 , wherein the acrylic adhesive is loaded with between 3 and 12% w/w granisetron. 
   
   
       15 . A patch according to  claim 14 , wherein the acrylic adhesive is loaded with between 4 and 10% w/w granisetron. 
   
   
       16 . A patch according to  claim 14 , wherein the acrylic adhesive is loaded with between 5 and 8% w/w granisetron. 
   
   
       17 . A patch according to  claim 16 , having a level of between 6% and 7.7% w/w of granisetron. 
   
   
       18 . A patch according to  claim 1 , wherein, at an acrylic adhesive loading of 6% w/w of active granisetron, the acrylic adhesive has a surface area of between 10 and 100 cm 2 . 
   
   
       19 . A patch according to  claim 18 , wherein the acrylic adhesive has a surface area of between 15 and 50 cm 2 . 
   
   
       20 . A patch according to  claim 1 , wherein no crystallisation is observed after one month storage at room temperature and pressure. 
   
   
       21 . A patch according to  claim 1 , wherein the granisetron content of said patch remains substantially unchanged when stored at 25° C. for at least six weeks. 
   
   
       22 . A patch according to  claim 1 , wherein the granisetron content of said patch remains substantially unchanged when stored at 40° C. for at least six weeks. 
   
   
       23 . A patch according to  claim 1 , for the treatment and/or prophylaxis of chemically induced emesis. 
   
   
       24 . A patch according to  claim 23 , wherein the emesis is acute. 
   
   
       25 . A patch according to  claim 23 , wherein the emesis is delayed. 
   
   
       26 . A patch according to  claim 1 , for the treatment and/or prophylaxis of emesis associated with fractionated chemotherapy. 
   
   
       27 . A patch according to  claim 1 , for the treatment and/or prophylaxis of postoperative nausea and vomiting. 
   
   
       28 . A patch according to  claim 1 , for the treatment and/or prophylaxis of nausea and vomiting associated with radiotherapy. 
   
   
       29 . A patch according to  claim 1 , for the treatment and/or prophylaxis of nausea and vomiting associated with fractionated cancer therapy. 
   
   
       30 . A patch according to  claim 1 , for the treatment and/or prophylaxis of chemotherapy-induced nausea and vomiting. 
   
   
       31 . A patch according to  claim 1 , for the treatment and/or prophylaxis of a condition selected from the group consisting of one or more of: pruritus, fibromyalgia and pain associated therewith, migraine, anxiety, cognitive and psychotic disorders, depression, schizophrenia, psychosis in postnatal depression, irritable bowel syndrome, alcoholism, obstructive sleep disturbed breathing, motion sickness, loss of cognitive function, urinary incontinence, dyskinesia, systemic lupus erythematosus, drug-induced pruritus, premature ejaculation, eating disorders, obsessive compulsive disorder, gastric motility disorders, chronic fatigue syndrome, dyspepsia and cocaine dependence. 
   
   
       32 . A patch according to  claim 1 , incorporating no plasticizers or permeation enhancers. 
   
   
       33 . A method for the treatment and/or prophylaxis of any form of nausea or emesis associated with 5-HT 3  receptor activity in a patient in need thereof, said method comprising applying an adhesive patch according to  claim 1  to the skin of the patient. 
   
   
       34 . A method for the treatment and/or prophylaxis of chemotherapy induced nausea and vomiting in a patient in need thereof, said method comprising applying an adhesive patch according to  claim 1  to the skin of the patient. 
   
   
       35 . A method for the treatment and/or prophylaxis of a patient having, or susceptible to, a condition selected from the group consisting of:
 pruritus, fibromyalgia and pain associated therewith, migraine, anxiety, cognitive and psychotic disorders, depression, schizophrenia, psychosis in postnatal depression, irritable bowel syndrome, alcoholism, obstructive sleep disturbed breathing, motion sickness, loss of cognitive function, urinary incontinence, dyskinesia, systemic lupus erythematosus, drug-induced pruritus, premature ejaculation, eating disorders, obsessive compulsive disorder, gastric motility disorders, chronic fatigue syndrome, dyspepsia and cocaine dependence,   said method comprising applying an adhesive patch according to  claim 1  to the skin of the patient.